Hiroyuki Tsutsui1, Shin-Ichi Momomura2, Akira Yamashina3, Hiroaki Shimokawa4, Yasuki Kihara5, Yoshihiko Saito6, Nobuhisa Hagiwara7, Hiroshi Ito8, Masafumi Yano9, Kazuhiro Yamamoto10, Junya Ako11, Takayuki Inomata12, Yasushi Sakata13, Takashi Tanaka14, Yasushi Kawasaki14. 1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University. 2. Cardiovascular Division, Jichi Medical University, Saitama Medical Center. 3. Department of Cardiology, Tokyo Medical University. 4. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine. 5. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences. 6. First Department of Internal Medicine, Nara Medical University. 7. Department of Cardiology, Tokyo Women's Medical University. 8. Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. 9. Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine. 10. Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University. 11. Cardiovascular Medicine, Kitasato University. 12. Cardiovascular Medicine, Kitasato University Kitasato Institute Hospital. 13. Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University. 14. Department of Clinical Development, Ono Pharmaceutical Co., Ltd.
Abstract
BACKGROUND:Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results: Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760). CONCLUSIONS: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.
RCT Entities:
BACKGROUND: Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results:Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760). CONCLUSIONS: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.
Authors: Mathias Maagaard; Emil Eik Nielsen; Naqash Javaid Sethi; Ning Liang; Si-Hong Yang; Christian Gluud; Janus Christian Jakobsen Journal: BMJ Evid Based Med Date: 2021-11-17